Aldehyde Dehydrogenase-2 Attenuates Myocardial Remodeling and Contractile Dysfunction Induced by a High-Fat Diet

• Main Authors: Chuanbao Li, Xiaoxing Li, Ying Chang, Lang Zhao, Baoshan Liu, Shujian Wei, Feng Xu, Yun Zhang, Yuguo Chen
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2018-08-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Metabolic syndrome; Myocardial remodeling; Apoptosis; ALDH2; Mice
• Online Access: https://www.karger.com/Article/FullText/492506
• ISSN: 1015-8987; 1421-9778

Background/Aims: Consumption of a high-fat (HF) diet exacerbates metabolic cardiomyopathy through lipotoxic mechanisms. In this study, we explored the role of aldehyde dehydrogenase-2 (ALDH2) in myocardial damage induced by a HF diet. Methods: Wild-type C57 BL/6J mice were fed a HF diet or control diet for 16 weeks. ALDH2 overexpression was achieved by injecting a lentiviral ALDH2 expression vector into the left ventricle. Results: Consumption of a HF diet induced metabolic syndrome and myocardial remodeling, and these deleterious effects were attenuated by ALDH2 overexpression. In addition, ALDH2 overexpression attenuated the cellular apoptosis and insulin resistance associated with a HF diet. Mechanistically, ALDH2 overexpression inhibited the expression of c-Jun N-terminal kinase (JNK)-1, activated protein 1 (AP-1), insulin receptor substrate 1 (IRS-1), 4- hydroxynonenal, caspase 3, transforming growth factor β1, and collagen I and III, and enhanced Akt phosphorylation. Conclusion: ALDH2 may effectively attenuate myocardial remodeling and contractile defects induced by a HF diet through the regulation of the JNK/AP-1 and IRS-1/Akt signaling pathways. Our study demonstrates that ALDH2 plays an essential role in protecting cardiac function from lipotoxic cardiomyopathy.